Cancer is the second-leading cause of death in the United States and is a serious public health concern. The current generation of cytotoxic chemotherapeutic agents used for the treatment of cancer is not curative for a majority of patients. For many cancer patients, the use of chemotherapy extends patient-life by only a few months and often results in serious side effects that reduce the quality of life.
Anticancer drugs that are utilized for cancer chemotherapy include cytotoxic nucleoside analogs (Pratt et al., “Antimetabolites” in The Anticancer Drugs, 2nd ed. Oxford University Press, New York. pp. 69-107 (1994)), such as analogs of the four nucleotides that are the principal components of DNA. Examples of cytotoxic analogs include the fluoropyrimidines (FPs) such as 5FU and FdU, which are analogs of Ura and dU, the precursor for dT, the arabinosyl nucleotides AraC and AraA, which are analogs of dC and dA, respectively, dFdC (gemcitabine), which is an analog of dC, and 6-mercaptopurine, which is an analog of dI, the precursor of dG.